We identified the - to our knowledge - first RNA binding protein without helicase activity that promotes translation of its target mRNAs. The CCHC-Zinc Finger, Nucleic Acid Binding Protein (CNBP) is a eukaryote-conserved nucleic-acid binding protein required in mammals for embryonic development. It contains seven CCHC-type zinc-finger domains and was suggested to act as a nucleic acid chaperone, as well as a transcription factor. Here, we identify all CNBP isoforms as cytoplasmic, messenger RNA (mRNA)-binding proteins. Using PAR-CLIP, we mapped its binding sites on RNA at nucleotide-level resolution on a genome-wide scale and found that CNBP interacted with 4178 mRNAs in a human cell line, preferentially at a G-rich motif close to the AUG start codon on mature mRNAs. Loss- and gain-of-function analyses coupled with system-wide RNA and protein quantification revealed that CNBP did not affect RNA abundance, but rather promoted translation of its targets. This is consistent with an RNA chaperone function of CNBP helping to resolve secondary structures, thus promoting translation. The impact of sequence-specific translational regulatory events controlled by RBPs cannot be studied by standard mRNA quantification at a systems-wide scale. Thus, the study of translational regulation affords our group the opportunity to become experts in state-of-the-art methods measuring translation efficiency, including ribosome profiling (Ingolia et al., 2009) and/or approaches to measuring protein abundance, including SILAC and iTRAQ (Ross et al., 2004; Schwanhausser et al., 2009). Combined with the biochemical assays established for the study of CNBP these protocols will allow us to dissect the molecular function of one of the most abundant RBPs in mammalian cells and tissues, YBX1, which we are implicating in translational regulation processes.